Treatment with a halved dose of antipsychotics in patients with schizophrenia who relapse while receiving high-dose antipsychotic therapy

Abstract

This study proposed and discussed a new treatment for patients with schizophrenia who relapse while receiving high-dose antipsychotic therapy. There is no drug therapy available for such patients. However, antipsychotic dose reduction by half may lead to remission. The positive symptoms of schizophrenia relate to increased striatal presynaptic dopamine availability and chaotic phasic firing of dopaminergic neurons in the striatum. Dopamine levels and its function in dopamine receptors show an inverted U-shaped curve relationship, which indicates that excessively high or low dopamine levels result in decreased dopamine activation. A halved dose of antipsychotics leads to excessive increase in subcortical dopamine levels and decreased dopamine function, resulting in the improvement of positive symptoms. Furthermore, there is a negative correlation between subcortical dopamine activity and the prefrontal cortex function; therefore, reduced mesostriatal dopamine activity may lead to increased prefrontal cortex function. The recovery of prefrontal cortex function may minimize impulsive or risk behaviors. The incidence of adverse events is similar after abrupt withdrawal or tapering of antipsychotics, except for the emergence of withdrawal dyskinesia. A halved dose of antipsychotics is effective for patients with schizophrenia who relapse while receiving high-dose antipsychotic therapy. Thus, we investigated whether an abrupt change to halved dose of antipsychotics improves positive symptoms and evaluated the efficacy of such treatment.